How GLP-1 Drugs Are Shaping the Future of Weight Loss and Mood, Even for Mental Health

Key Takeaways

• GLP-1 drugs may protect brain cells from damage, potentially reducing the risk of neurodegenerative diseases like Alzheimer's.
• GLP-1 drugs offer combined treatment for people with both metabolic and psychiatric conditions, such as depression. 
• GLP-1 drugs are being discussed as a new class of antidepressants, potentially. They may be able to mitigate the weight gain that may be caused by using traditional antidepressants.
• The effects of GLP-1 drugs on mental and neurological health are mixed. Some GLP-1 users experience side effects, including increased depression, anxiety, and suicidal ideation.
• We need more randomized placebo-controlled clinical trials to fully understand GLP-1's long-term impact on mental health and its role in psychiatric treatments.

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What Are GLP-1 Drugs?

Glucagon-like peptide-1 (GLP-1) is a key hormone in regulating blood sugar, metabolism, appetite, and satiety. Gut cells produce GLP-1 in response to a meal. Then, GLP-1 affects other hormones, including insulin and glucagon, which regulate blood glucose levels. It also slows down digestion and decreases appetite.

GLP-1 drugs are ‌glucagon-like peptide-1 receptor agonists (GLP-1 RAs). This means they act like the GLP-1 hormone, binding to its receptor and making the body respond as if it were producing GLP-1.¹

GLP-1 drugs were first developed to manage type 2 diabetes mellitus. Now, they are widely used as pharmacological treatments for weight loss due to their effects on glycemic control, appetite, and satiety.

Various GLP-1 drugs are available:

• Semaglutide injections (Ozempic, Wegovy)
• Semaglutide tablets (Rybelsus)
• Dulaglutide (Trulicity) 
• Exenatide (Byetta) 
• Exenatide Extended Release (Bydureon BCise) 
• Liraglutide (Victoza, Saxenda) 
• Lixisenatide (Adlyxin) 
• Tirzepatide (Mounjaro, Zepbound)

The most widely known GLP-1 agonists include Ozempic, Rybelsus, and Wegovy. They all contain the active ingredient called semaglutide.

Other popular brands, such as Mounjaro and Zepbound, work a little differently than semaglutide. They contain the active ingredient called tirzepatide. These drugs not only act on GLP-1 receptors but also on GIP (glucose-dependent insulinotropic polypeptide). GIP is another hormone that helps improve both blood glucose control and fat metabolism.²

Some are FDA-approved only for the management of type 2 diabetes, while others are approved as weight loss medications. 

• Approved for type 2 diabetes management: Mounjaro, Ozempic, Rybelsus,  Trulicity, Byetta, Adlyxin, Victoza
• Approved for weight management: Wegovy, Zepbound, and Saxenda

How GLP-1s Influence Weight Loss

GLP-1 drugs change the direction of antidiabetic and weight loss treatments. GLP-1s cause weight loss through various mechanisms:³

Stimulating insulin production and inhibiting glucagon secretion

Insulin is produced when blood sugar levels are high. It allows sugar to enter cells, which brings blood sugar levels back to normal. Glucagon is produced when blood sugar levels are low. It signals the liver to release glucose, maintaining blood sugar levels. GLP-1 regulates blood sugar levels in a way that prevents big swings in blood sugar by influencing these hormones. Maintaining balanced blood sugar levels can aid in weight loss and diabetes management.

Slowing down digestion

Your stomach senses how much you eat. There are receptors that detect the distention of the stomach and communicate with the brain via nerves. The duration a meal stays in the stomach affects this distension and, therefore, the signaling to the brain. GLP-1 slows down digestion, increasing the time food remains in the stomach. This tells the brain to decrease food intake and hunger.

Decreasing appetite and increasing satiety

The brain plays a crucial role in regulating both appetite and satiety. The brain and body communicate through certain molecules and hormones. GLP-1 is one of the key hormones that signal the brain to stop eating when you’ve had a meal and feel full. GLP-1 binds to its receptors in the brain, triggering the release of molecules that reduce the desire to continue eating. GLP-1 drugs can also increase the effect of leptin (a hormone regulating satiety) in the brain and help regulate your appetite.

Furthermore, GLP-1 drugs improve metabolism and body weight by enhancing fat metabolism, reducing inflammation, and increasing heat production.

The Unexpected Mental Health Effects of GLP-1 Drugs

GLP-1 drugs weren’t developed to target mental health conditions. However, recent studies discuss how GLP-1 drugs can improve mental health by improving mood, cognition, and addictive behaviors. This could partly be a result of increased quality of life and mental well-being, as well as changes in brain physiology.⁴

Because GLP-1 RAs can cross the blood-brain barrier, they have the potential to influence areas involved in psychiatric disorders and cognitive regulation. 

Animal studies have demonstrated that GLP-1 receptor agonists (GLP-1 RAs) exert protective effects on nerve cells (neurons) in the brain and nervous system, thereby helping to prevent damage, degeneration, and cell death. Additionally, GLP-1 RAs have been shown to improve learning and memory in rodents with Alzheimer's disease. ⁵

There is a growing interest in how GLP-1 RAs may support mental health beyond glucose regulation.  More and more people are sharing their experiences about the mental benefits of using GLP-1 medications. A study analyzed various online platforms and found that people reported mixed effects. Some reported improvements due to weight loss, while others experienced it triggering insomnia, anxiety, depression, and addictive behaviors.⁶

What Science Says: Clinical Studies & Observations

Research on GLP-1 medications shows potential benefits beyond weight loss, including improvements in mental health and cognitive function. Studies suggest these drugs can reduce depression, lower dementia risk, and even help with alcohol use disorder:

• A meta-analysis showed that using GLP-1 medications significantly decreased participants' scores on depression rating scales. These scales are commonly used to assess the severity of depressive symptoms.⁷
• Another meta-analysis showed that diabetic patients using GLP-1 RAs had a reduced risk of developing dementia.⁸
• In a clinical trial, patients with type 2 diabetes who used GLP-1 RA showed improvements in all cognitive tests, particularly in memory and attention.⁹
• A large cohort study with 83,835 people found that those taking semaglutide had a 50% to 56% lower risk of developing or relapsing into alcohol use disorder over one year, compared to people using other weight loss drugs that are not GLP-1 medications.¹⁰

These findings suggest that GLP-1 medications may offer potential treatments for people with both metabolic and psychiatric health conditions.

While other studies show that GLP-1 drugs can negatively affect mental health:

• A case study reported that a person experienced adverse mood changes, difficulty sleeping, and loss of interest in activities previously found enjoyable, starting after 4 weeks of treatment with Ozempic (semaglutide). She had a history of depressive episodes. When she discontinued Ozempic, the symptoms improved within several weeks.¹¹

• A large study looked at the effects of various GLP-1 medications on psychiatric conditions in people with obesity. Results from 162,253 participants showed that those using a GLP-1 medication had a 195% higher risk for major depression, a 108% increased risk for anxiety, and a 106% elevated risk for suicidal behavior compared to those who didn’t use any GLP-1 medications. The GLP-1 drugs used by participants included Victoza, Saxenda, Ozempic, and Wegovy.¹²

These conflicting results show the need for more randomized controlled trials to clarify the benefits and potential adverse effects of GLP-1 RAs on mental and neurological health.

Additionally, the Food and Drug Administration (FDA) has reviewed reports of suicidality associated with GLP-1 RAs. However, the FDA concluded that there wasn’t a clear connection between the drug and these behaviors.¹³

Still, the agency continues to monitor the risk, as incidents have been reported in people using GLP-1 RAs. In the meantime, the FDA has advised healthcare professionals to watch for any signs of depression or suicidal thoughts in people using these medications, with extra caution for those with a history of mental illness.

Considerations and Concerns

Although GLP-1 medications can help some people when used under the guidance of a healthcare professional, they’re not magic pills. Before using GLP-1 medications, it's crucial to evaluate the potential risks and benefits for each individual to help prevent side effects and serious health risks.

As we discussed above, some clinical studies report that GLP-1 drugs can trigger mental health conditions. Some GLP-1 drugs also mention this in their prescription information. For example, Wegovy has a warning about the possibility of the drug triggering depression, suicidal thoughts, and behaviors. It also emphasizes that Wegovy should be avoided in people with active suicidal thoughts or a history of suicidal attempts.¹⁴

A study examined the FDA's Adverse Event Reporting System to evaluate reported side effects associated with GLP-1 drugs between the years 2004 and 2023. Among all reports, approximately 4.5% were linked to psychiatric side effects. The most commonly reported psychiatric side effects included self-induced vomiting, fear of eating, binge eating, insomnia-related conditions, fear of rejection, and stress.¹⁵

Therefore, the effects of GLP-1 drugs on mental health outcomes vary. More studies are needed to understand the long-term effects of GLP-1 medications on mental health and psychiatric conditions. You should consult a healthcare provider before starting GLP-1 medications. 

What This Means for the Future of Treatment

The effect of GLP-1 agonists on neurons holds promise for new treatments in psychiatry. They may also offer combined treatment for individuals with conditions affecting both metabolic and mental health, such as eating disorders.¹⁶

Besides, GLP-1 agonists may hold promise for the prevention of neurodegenerative conditions such as Alzheimer's and Parkinson's diseases.

However, we still don’t fully understand how GLP-1 agonists affect brain cells. Another challenge is that symptoms, brain physiology, and responses to interventions can vary widely across psychiatric conditions. This makes it challenging to optimize the use of GLP-1 agonists in each psychiatric condition. 

The Bottom Line

GLP-1 receptor agonists (GLP-1 RAs) may enhance cognition and help protect neurons by preventing damage, promoting new cell growth, and enhancing communication between brain cells. This points to a new direction for GLP-1 RAs as potential psychiatric treatments or as part of combination therapies for people with both obesity, diabetes, and psychiatric conditions such as depression.

However, some studies have also reported increased depression, anxiety, and suicidal thoughts in people using GLP-1 RAs.

We still do not fully understand how GLP-1 RAs affect brain cells or psychiatric conditions. If you are considering using GLP-1 medications for mental health and psychiatric conditions, consult your healthcare provider first.

Learn More With Signos’ Expert Advice

Continuous blood glucose monitoring (CGM) systems allow you to track your blood glucose levels throughout the day and night. You will see how your blood sugar levels change in response to your diet, physical activity, and other factors. 

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